Hepatitis B (HBV) causes viral Hepatitis that can further lead to chronic liver disease and increase the risk of liver cirrhosis and liver cancer (hepatocellular carcinoma). Worldwide, more than 2 billion people have been infected with HBV, around 360 million people are chronically infected and every year HBV infection causes more than one million deaths (World Health Organization, 2009). HBV can be spread by body fluids: e.g., from mother to child, by sex, and via blood products. Children born to HBV-positive mothers may be infected, unless vaccinated at birth.
At present, chronic HBV is primarily treated with nucleos(t)ides analogues (e.g., entecavir, tenofovir disoproxil fumarate (TDF)) that suppress the virus while the patient remains on treatment but do not eliminate the infection, even after many years of treatment. Once a patient starts taking nucleos(t)ide analogues, most must continue taking them or risk the possibility of a life threatening immune response to viral rebound. Further, nucleos(t)ide analogue therapy may lead to the emergence of antiviral drug resistance and, in rare cases, adverse events have been reported.
The only FDA approved alternative to nucleos(t)ide analogues is treatment with interferon-α (IFN-α) or pegylated interferon-α (PEG-IFN-α). Unfortunately, the adverse event incidence and profile of interferon-α can result in poor tolerability, and many patients are unable to complete therapy. Moreover, only a small percentage of patients are considered appropriate for interferon therapy, as only a small subset of patients who present with low viral loads and transaminitis greater than 2× the upper limit of normal are likely to have a sustained clinical response to a year's course of interferon therapy. As a result, interferon based therapies are used in only a small percentage of all diagnosed patients who elect for treatment.
Thus, current HBV treatments can range from palliative to benign neglect. Nucleos(t)ide analogues suppress virus production, treating the symptom, but leave the infection intact. Interferon-α has severe side effects and less tolerability among patients and is successful as a finite treatment strategy in only a small minority of patients.